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We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

This work introduces a method to tune a sequence-based generative model for molecular de novo design that through augmented episodic likelihood can learn to generate structures with certain specified desirable properties. We demonstrate how…

Artificial Intelligence · Computer Science 2017-08-30 Marcus Olivecrona , Thomas Blaschke , Ola Engkvist , Hongming Chen

Predicting the binding free energy between antibodies and antigens is a key challenge in structure-aware biomolecular modeling, with direct implications for antibody design. Most existing methods either rely solely on sequence embeddings or…

Biomolecules · Quantitative Biology 2025-08-28 Ciyuan Yu , Hongzong Li , Jiahao Ma , Shiqin Tang , Ye-Fan Hu , Jian-Dong Huang

Contrastive learning methods for time series anomaly detection (TSAD) heavily depend on the quality of negative sample construction. However, existing strategies based on random perturbations or pseudo-anomaly injection often struggle to…

Machine Learning · Computer Science 2026-03-20 Xiancheng Wang , Lin Wang , Zhibo Zhang , Rui Wang , Minghang Zhao

Structure-based drug design involves finding ligand molecules that exhibit structural and chemical complementarity to protein pockets. Deep generative methods have shown promise in proposing novel molecules from scratch (de-novo design),…

Quantitative Methods · Quantitative Biology 2021-11-09 Pavol Drotár , Arian Rokkum Jamasb , Ben Day , Cătălina Cangea , Pietro Liò

Structure-based drug design aims at generating high affinity ligands with prior knowledge of 3D target structures. Existing methods either use conditional generative model to learn the distribution of 3D ligands given target binding sites,…

Biomolecules · Quantitative Biology 2024-03-18 Yuwei Yang , Siqi Ouyang , Xueyu Hu , Mingyue Zheng , Hao Zhou , Lei Li

In this work, we introduce Auxiliary Discriminator Sequence Generative Adversarial Networks (ADSeqGAN), a novel approach for molecular generation in small-sample datasets. Traditional generative models often struggle with limited training…

Machine Learning · Computer Science 2025-09-15 Haocheng Tang , Jing Long , Beihong Ji , Junmei Wang

Adeno-associated viral (AAV) vectors are widely used delivery platforms in gene therapy, and the design of improved capsids is key to expanding their therapeutic potential. A central challenge in AAV bioengineering, as in protein design…

The emergence of 3D artificial intelligence-generated content (3D-AIGC) has enabled rapid synthesis of intricate geometries. However, a fundamental disconnect persists between AI-generated content and human-centric design paradigms, rooted…

Graphics · Computer Science 2025-08-29 Xiaoyang Huang , Bingbing Ni , Wenjun Zhang

Recent advancements in protein design have leveraged diffusion models to generate structural scaffolds, followed by a process known as protein inverse folding, which involves sequence inference on these scaffolds. However, these…

Biomolecules · Quantitative Biology 2025-02-27 Xingyi Zhang , Kun Xie , Ningqiao Huang , Wei Liu , Peilin Zhao , Sibo Wang , Kangfei Zhao , Biaobin Jiang

Antibodies are crucial proteins produced by the immune system in response to foreign substances or antigens. The specificity of an antibody is determined by its complementarity-determining regions (CDRs), which are located in the variable…

Biomolecules · Quantitative Biology 2024-01-11 Cheng Tan , Zhangyang Gao , Lirong Wu , Jun Xia , Jiangbin Zheng , Xihong Yang , Yue Liu , Bozhen Hu , Stan Z. Li

We explore recurrent encoder multi-decoder neural network architectures for semi-supervised sequence classification and reconstruction. We find that the use of multiple reconstruction modules helps models generalize in a classification task…

Computer Vision and Pattern Recognition · Computer Science 2018-07-12 Félix G. Harvey , Julien Roy , David Kanaa , Christopher Pal

Designing novel protein sequences for a desired 3D topological fold is a fundamental yet non-trivial task in protein engineering. Challenges exist due to the complex sequence--fold relationship, as well as the difficulties to capture the…

Machine Learning · Computer Science 2021-06-25 Yue Cao , Payel Das , Vijil Chenthamarakshan , Pin-Yu Chen , Igor Melnyk , Yang Shen

Generative models for structure-based molecular design hold significant promise for drug discovery, with the potential to speed up the hit-to-lead development cycle, while improving the quality of drug candidates and reducing costs. Data…

Machine Learning · Statistics 2022-04-25 Lucian Chan , Rajendra Kumar , Marcel Verdonk , Carl Poelking

The design and optimization of antibodies requires an intricate balance across multiple properties. Protein inverse folding models, capable of generating diverse sequences folding into the same structure, are promising tools for maintaining…

A key step in reverse engineering neural networks is to decompose them into simpler parts that can be studied in relative isolation. Linear parameter decomposition -- a framework that has been proposed to resolve several issues with current…

Machine Learning · Computer Science 2025-09-05 Lucius Bushnaq , Dan Braun , Lee Sharkey

Optimizing combinatorial structures is core to many real-world problems, such as those encountered in life sciences. For example, one of the crucial steps involved in antibody design is to find an arrangement of amino acids in a protein…

Training-free high-resolution (HR) image generation has garnered significant attention due to the high costs of training large diffusion models. Most existing methods begin by reconstructing the overall structure and then proceed to refine…

Computer Vision and Pattern Recognition · Computer Science 2024-12-10 Yuming Li , Peidong Jia , Daiwei Hong , Yueru Jia , Qi She , Rui Zhao , Ming Lu , Shanghang Zhang

The increasing size of deep learning models has made distributed training across multiple devices essential. However, current methods such as distributed data-parallel training suffer from large communication and synchronization overheads…

Machine Learning · Computer Science 2025-02-10 Cabrel Teguemne Fokam , Khaleelulla Khan Nazeer , Lukas König , David Kappel , Anand Subramoney

Antimicrobial peptides (AMPs) are promising therapeutic approaches against drug-resistant pathogens. Recently, deep generative models are used to discover new AMPs. However, previous studies mainly focus on peptide sequence attributes and…

Biomolecules · Quantitative Biology 2023-08-22 Danqing Wang , Zeyu Wen , Fei Ye , Lei Li , Hao Zhou